Adults with acute lymphoblastic leukemia and translocation (1;19) abnormality have a favorable outcome with hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone alternating with methotrexate and high‐dose cytarabine chemotherapy

Chromosomal abnormalities in acute leukemia determine the disease pathophysiology and patient prognosis. Treatment of childhood acute lymphoblastic leukemia (ALL) results in high cure rates of 70% to 90%. Adults with ALL achieve high complete remission rates of 80% to 90%; however, cure rates are only 30% to 40%.1 A major difference between childhood and adult ALL is the frequency of various cytogenetic subcategories. A hyperdiploid karyotype, which is favorable, is observed in 30% of children compared with 2% to 5% of adults. Another favorable category is a translocation involving chromosomes 12 and 21, t(12;21), which results in the TEL-AML1 fusion gene.2 The latter is the most common molecular lesion in childhood ALL but is uncommon in adult ALL (range, 3%–4%).3,4 The t(9;22), or the Philadelphia chromosome (Ph) (an unfavorable cytogenetic subset), is common in adult ALL (25%) but is rare in childhood ALL (<5%).5,6 One difficulty with elucidating the prognostic influence of certain cytogenetic abnormalities in ALL has been the rarity of the disease7 coupled with the low frequency of specific abnormalities. One recurring translocation in both children and adults is t(1;19)(q23;p13). It results in a fusion of the transcription factor 3 gene TCF3 (E2A) at 19p13 with the pre-B-cell leukemia homeobox gene PBX1 at 1q23, creating a TCF3-PBX1 fusion gene that encodes a protein with transforming properties. The E2A gene encodes 2 transcription factors, E12 and E47, which, in turn, bind to enhancer elements in the immunoglobulin κ or IGK gene and regulatory elements of other genes. PBX1 is a homeobox gene (HOX) on chromosome 1. E2A/PBX1 fusion messenger RNAs are formed and code for chimeric proteins that consist of the transcriptional activating domain of E12/E47 and DNA-binding domains of PBX1.8,9 The E2a/Pbx1 fusion protein may promote leukemogenesis by the transactivation of several genes normally not expressed in lymphoid tissues.10 The t(1;19) occurs in 2 forms: 1) a reciprocal translocation t(1;19)(q23;p13) or, more often, 2) an unbalanced form characterized by 2 normal chromosomes 1 and 19 and a rearranged chromosome 19, der(19)t(1,19)(q23;p13). In some studies, patients with the reciprocal translocation had a worse outcome.11 Children with t(1;19) who were treated on conventional antimetabolite-based therapy protocols had poor outcomes.12 Newer intensified regimens have improved prognosis, but patients with a balanced t(1;19) translocation still have an adverse prognosis.13 In the current study, we reviewed the outcome of adults with ALL and t(1;19) who received the hyperfractionated cyclophosphamide, vincristine, doxorubicin (Adriamycin), and dexamethasone alternating with methotrexate and high-dose cytarabine (hyper-CVAD) regimen.14